As indicated by NCMRR, the primary goal of patient-oriented research is to develop the "scientific knowledge necessary to enhance the health, productivity, independence, and quality-of-life of people with disabilities." Multiple sclerosis is a prevalent and chronic neurologic disease associated with memory dysfunction and cerebral inefficiency, which encumber productivity, limit independence, and frequently diminish the quality of life among many young and middle aged persons with MS. Despite this, the etiology of memory dysfunction in MS is very poorly explained by brain pathology alone, perhaps due to yet undiscovered protective factors. This CDA project will investigate the role of cognitive reserve in protecting persons with MS from disease- related memory dysfunction and cerebral inefficiency. Cognitive reserve theory proposes that enriching life experiences (such as educational attainment) increase the capacity and efficiency of neural networks. When cerebral functioning is challenged by neurologic disease, individuals with more cognitive reserve are better able to cope with the increased cognitive demands. This has been demonstrated in Alzheimer's Disease and other neurologic conditions, but the current proposal is the first to directly investigate cognitive reserve in MS. During the mentored phase of this grant, I will investigate whether cognitive reserve protects persons with MS from the deleterious effects of brain pathology on learning and memory. My primary training aim is to develop competence in fMRI. Combined with the rich research training at KMRREC, fMRI training will enable me to investigate the protective role of cognitive reserve on cerebral efficiency in MS, and prepare me for a career as an independent patient-oriented researcher utilizing this innovative technology. These projects represent the first steps in my plan to pursue a more comprehensive research program directed toward (1) identifying sources of protective cognitive reserve and (2) using these sources as a means to reduce the negative impact of neurologic disease on quality of life for persons with MS in particular, and neurologic patients in general. This Career Development Award is a necessary and essential step in my plans to become an independent patient-oriented researcher. PUBLIC HEALTH RELEVANCE: Demonstration of the protective role of cognitive reserve in MS will fill wide gaps in the MS and cognitive reserve literatures. Identification of low cognitive reserve as a risk factor will improve prognoses of cognitive dysfunction, thereby promoting early intervention cognitive rehabilitation. I will pursue a program of research to identify other modifiable sources of reserve, which can then be utilized for preventative neurorehabilitation.